Premium
Diversity of GABA A receptor synaptic currents on individual pyramidal cortical neurons
Author(s) -
Ing Timothy,
Poulter Michael O.
Publication year - 2007
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2007.05331.x
Subject(s) - inhibitory postsynaptic potential , gabaa receptor , neuroscience , chemistry , amplitude , zolpidem , receptor , biology , physics , biochemistry , pharmacology , insomnia , quantum mechanics
Miniature GABA A receptor‐mediated inhibitory postsynaptic currents (mIPSCs) in cortical pyramidal neurons have previously been categorized into two types: small amplitude mIPSCs with a mono‐exponential deactivation (mono‐mIPSCs) and relatively larger mIPSCs with bi‐exponential deactivation (bi‐mIPSCs). The aim of this study was to determine if the GABA A channels that underlie these mIPSCSs are molecularly distinct. We found, using non‐stationary noise analysis, that the difference in their amplitude could be not accounted for by their single channel conductance (both were 40 pS). Next, using α subunit selective GABA A receptor modulators, we examined the identity of the α subunits that may be expressed in the synapses that give rise to these mIPSCs. Zolpidem (100 and 500 n m , α 1 selective) affected the deactivation of a subset of the mono‐mIPSCs, indicating that α 1 subunits are not highly expressed in these synapses. However, zolpidem (100 n m ) prolonged the deactivation of all bi‐mIPSCs, indicating a high abundance of α 1 subunits in these synapses. SB‐205384 (α 3 selective) had no effect on the mono‐mIPSCs but the bi‐mIPSCs were prolonged. Furosemide (α 4 selective) reduced the amplitude of only the mono‐mIPSCs. L655,708 (α 5 selective) reduced the amplitude of both populations and shortened the duration of the mono‐mIPSCs. Finally, we found that the neuroactive steroid pregesterone sulphate reduced the amplitude of both mIPSC types. These results provide pharmacological evidence that synapses on cortical pyramidal neurons are molecularly distinct. The purpose of these different types of synapses may be to provide different inhibitory timing patterns on these cells.